PROSITE documentation PDOC51285AGC-kinase C-terminal domain profile
The AGC (cAMP-dependent, cGMP-dependent and protein kinase C) protein kinase family embraces a collection of protein kinases that display a high degree of sequence similarity within their respective kinase domains. AGC kinase proteins are characterized by three conserved phosphorylation sites that critically regulate their function. The first one is located in an activation loop in the center of the kinase domain. The two other phosphorylation sites are located outside the kinase domain in a conserved region on its C-terminal side, the AGC-kinase C-terminal domain. These sites serves as phosphorylation-regulated switches to control both intra- and inter-molecular interactions. Without these priming phosphorylations, the kinases are catalytically inactive [1,2,3].
Several structures of the AGC-kinase C-terminal domain have been solved (see for example <PDB:1O6L>). The first phosphorylation site is located in a turn motif the second one at the end of the domain in an hydrophobic pocket. In PKB the phosphorylated hydrophobic motif engages a hydrophobic groove within the N-lobe of the kinase domain which orders α helices close to the active site [4].
The profile we developed covers the entire AGC-kinase C-terminal domain.
Note:In some AGC kinases the C-terminal AGC-kinase domain is also known as the PIF domain.
Last update:December 2006 / First entry.
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PROSITE method (with tools and information) covered by this documentation:
| 1 | Authors | Newton A.C. |
| Title | Regulation of the ABC kinases by phosphorylation: protein kinase C as a paradigm. | |
| Source | Biochem. J. 370:361-371(2003). | |
| PubMed ID | 12495431 | |
| DOI | 10.1042/BJ20021626 |
| 2 | Authors | Parker P.J. Parkinson S.J. |
| Title | AGC protein kinase phosphorylation and protein kinase C. | |
| Source | Biochem. Soc. Trans. 29:860-863(2001). | |
| PubMed ID | 11709088 |
| 3 | Authors | Mora A. Komander D. van Aalten D.M. Alessi D.R. |
| Title | PDK1, the master regulator of AGC kinase signal transduction. | |
| Source | Semin. Cell Dev. Biol. 15:161-170(2004). | |
| PubMed ID | 15209375 |
| 4 | Authors | Yang J. Cron P. Good V.M. Thompson V. Hemmings B.A. Barford D. |
| Title | Crystal structure of an activated Akt/protein kinase B ternary complex with GSK3-peptide and AMP-PNP. | |
| Source | Nat. Struct. Biol. 9:940-944(2002). | |
| PubMed ID | 12434148 | |
| DOI | 10.1038/nsb870 |
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